Vertebrate blood contains a number of components, including plasma, platelets, and red blood cells. Blood also contains components such as various types of white blood cells (leukocytes), and proteins of the complement system, that provide for combating infection.
Blood components may be separated, and further processed, for a variety of uses, particularly as transfusion products. Illustratively, red blood cells (typically concentrated as packed red blood cells), plasma, and platelets (typically concentrated as platelet concentrate), can be separately administered to different patients. Some components, e.g., plasma and/or platelets, can be pooled before administration, and plasma can be fractionated to provide enriched components to treat disease.
While leukocytes combat infection and engulf and digest invading microorganisms and debris, the presence of leukocytes in transfusion products can be undesirable, since, for example, they may cause adverse effects (e.g., a febrile reaction) in the patient receiving the transfusion. Additionally, the presence of a significant level of red blood cells in some transfusion products (particularly if the transfusion products have been pooled) can lead to an adverse immune response by the patient.
The processing of blood to produce transfusion products can lead to the activation of the complement system, that acts on its own and in cooperation with antibodies in defending the host against infection. The complement system is composed of a series of plasma-borne blood proteins (proenzymes) that are sequentially activated in a series of reactions. The proteins are activated in cascade fashion, i.e., the output of one reaction is the input for the next. The cascade ultimately generates a terminal five-protein membrane attack complex (MAC, C5b-9), whose physiological function is protection of the host from invading microorganisms. The MAC causes lysis of the microorganisms.
While the complement system is generally beneficial in protecting the host, the presence of the various activated or activatable blood proteins (and fragments thereof) can be undesirable, particularly when these proteins and/or fragments are present in blood or blood components used for transfusion. For example, activation can lead to the administration of biologically active complement fragments such as C3a and its metabolite, C3a des Arg77. Transfusing activated complement into a patient can cause adverse affects such as anaphylactoid reactions, platelet aggregation, and/or immune suppression.
Accordingly, there is a need in the art for a filter for use with biological fluids such as blood and blood components, particularly for the production of plasma-rich blood products, that minimizes the contamination of the plasma-rich blood product by leukocytes, as well by other materials such as platelets and/or red blood cells. There is also a need for a filter that depletes complement and/or prevents the activation of complement in biological fluids such as plasma-rich blood products. These and other advantages of the present invention will be apparent from the description as set forth below.